Emphysema, together with asthma and chronic bronchitis, represent a disease complex known as chronic obstructive pulmonary disease (COPD). These three diseases are related in that they each cause difficulty breathing and, in most instances, progress over time. There are substantial differences, however, in their etiology, pathology, and prognosis. For example, while asthma and chronic bronchitis are diseases of the airways, emphysema is associated with irreversible, destructive changes in lung parenchyma distal to the terminal bronchioles. Cigarette smoking is the primary cause of emphysema; the smoke triggers an inflammatory response within the lung, which is associated with an activation of both elastase and matrix metalloproteinases (MMPs). These enzymes degrade key proteins that make up the tissue network of the lungs (Shapiro et al., Am. J. Resp. Crit. Care Med. 160:s29-s32, 1999; Hautamaki et al., Science 277:2002-2004, 1997). In fact, the pathological determinant of lung dysfunction in emphysema is the progressive destruction of elastic tissue, which causes loss of lung recoil and progressive hyper-expansion.
Almost two million Americans and at least three times that many individuals worldwide suffer from emphysema (see American Thoracic Society, Am. J. Resp. Crit. Care Med. 152:s77-s121, 1995). The average patient with emphysema reaches a critical level of compromise by about the age of 60 and, at that point, often begins to experience symptoms such as shortness of breath. In addition, functional capacity becomes reduced, quality of life is compromised, and the frequency of hospitalization is increased. Despite aggressive public health initiatives, cigarette smoking remains common, and emphysema will likely remain a major public health problem well into the new millennium.
Even though emphysema is a distinct condition, the therapies that have been developed to treat it are patterned after those used to treat asthma and chronic bronchitis. The treatments can be grouped into five categories: (1) inhaled and oral medications that help open narrowed or constricted airways by promoting airway muscle relaxation; (2) inhaled and oral medications that reduce airway inflammation and secretions; (3) oxygen therapy, which is designed to delay or prevent the development of pulmonary hypertension and cor pulmonale (right ventricular failure) in patients with chronic hypoxemia; (4) exercise programs that improve cardiovascular function, functional capacity, and quality of life; and (5) smoking cessation programs to delay the loss of lung function by preventing progression of smoking-related damage (Camilli et al., Am. Rev. Resp. Dis. 135:794-799, 1987). Although each of these approaches has been shown to have beneficial effects in this patient population, only oxygen therapy and smoking cessation significantly alter the natural history of this disease (Nocturnal Oxygen Therapy Trial Group, Ann. Intern. Med. 93:391, 1980).
Surgical therapy has recently been introduced as an adjunct to the medical treatments described above, and the results have been impressive. The surgical approach, known as lung volume reduction surgery (LVRS), improves lung function, exercise capacity, breathing symptoms, and quality of life in the majority of emphysema patients who meet designated selection criteria (Cooper et al., J. Thorac. Cardiovasc. Surg. 109:106-116, 1995). In LVRS, damaged, hyper-inflated lung is removed, and this is believed to provide a better fit between the over-expanded lung and the more normal sized chest wall. The fraction of the lung that remains within the chest cavity can better expand, and this increases the proportion of lung that can effectively contribute to ventilation (Fessler et al., Am. J. Resp. Crit. Care Med. 157:715-722, 1998). Recoil pressures increase, and expiratory flows improve. To date, LVRS is the only treatment that directly addresses lung hyper-expansion, which is the primary physiological abnormality of emphysema. Unfortunately, the benefits of LVRS may tend to decline over time (see Gelb et al., Am. J. Resp. Crit. Care Med. 163:1562-1566, 2001).